In 2012, a study from University of California at San Diego researchers discovered that “free fatty acids created during the digestion of infant formula cause cellular death that may contribute to necrotizing enterocolitis, a severe intestinal condition that is often fatal and occurs most commonly in premature infants.”1

Their report was published online in the journal Pediatric Research.


Scientists have known for a long time that premature infants fed formula are more likely to develop necrotizing enterocolitis than those fed breast milk. In fact, it’s the leading cause of death. However, until now scientists didn’t know why.

Based on in vitro tests comparing the digestion of fresh human breast milk and nine different infant formulas, the team found that “the intestine is leakier at birth, particularly for preterm infants, which could be why they are more susceptible to necrotizing enterocolitis.” (Partially digested food in a mature, adult intestine is capable of killing cells due to the presence of free fatty acids which have a “detergent” capacity that damages cell membranes. But the intestines of healthy adults and older children also have a mature mucosal barrier that may prevent damage due to free fatty acids in the first place.)

“Therefore, the researchers wanted to know what happens to breast milk as compared to infant formula when they are exposed to digestive enzymes. They “digested,” in vitro, infant formulas marketed for full-term and preterm infants as well as fresh human breast milk using pancreatic enzymes or fluid from an intestine. They then tested the formula and milk for levels of free fatty acids. They also tested whether these fatty acids killed off three types of cells involved in necrotizing enterocolitis: epithelial cells that line the intestine, endothelial cells that line blood vessels, and neutrophils, a type of white blood cell that is a kind of “first responder” to inflammation caused by trauma in the body.

Overwhelmingly, the digestion of formula led to cellular death, or cytotoxicity — in less than 5 minutes in some cases — while breast milk did not. For example, digestion of formula caused death in 47 percent to 99 percent of neutrophils while only 6 percent of them died as a result of milk digestion. The study found that breast milk appears to have a built-in mechanism to prevent cytotoxicity. The research team believes most food, like formula, releases high levels of free fatty acids during digestion, but that breast milk is digested in a slower, more controlled, process.”2

Over the last decade, neonatal intensive care units have largely moved away from formula and pushed breast milk as the best option. However, breastfeeding a premie can be challenging if not physically impossible and supplies of donor breast milk are limited. Researchers believe that “less cytotoxic milk replacements will need to be designed”3 in order to lower the risk of cell damage and necrotizing enterocolitis.


Breastmilk is still best. And this study shows that. But the study also found that breastfeeding may be of benefit to full-term infants at high risk of disorders “associated with gastrointestinal problems and more leaky intestines, such as autism spectrum disorder.”4


The next step will be to find out if these results can be replicated in animal studies and whether or not intervention can prevent free fatty acids from causing intestinal damage or death from necrotizing enterocolitis.

Sources and References

  1. Science Daily, December 12, 2012.
  2. Science Daily, December 12, 2012.
  3. Science Daily, December 12, 2012.
  4. Science Daily, December 12, 2012.